Elsevier

Neuroscience Letters

Volume 132, Issue 2, 11 November 1991, Pages 255-258
Neuroscience Letters

Blockade of the AMPA receptor prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats

https://doi.org/10.1016/0304-3940(91)90314-JGet rights and content

Abstract

The cytoprotective effect of NBQX, a selective AMPA receptor antagonist, was tested following 10 min of severe forebrain ischemia using the 4-vessel occlusion model. Immediately, and at 15 and 30 min following reperfusion, adult Wistar rats received intraperitoneal injections of either saline (n = 5), 1 mg lithium chloride (n = 17) or 30 mg/kg of the lithium salt of NBQX (n = 18). In saline-treated animals 82 ± 12% of CA1 hippocampal neurons were lost. Of those treated with lithium 70 ± 23% were injured, while those given NBQX sustained only 40 ± 34% CA1 necrosis (P < 0.01). Twelve of 18 NBQX-treated animals had less than 30% CA1 injury as compared with 1 of 17 lithium-treated animals. The AMPA receptor may play a more important role than the NMDA receptor in selective ischemic necrosis of hippocampal neurons.

References (25)

  • T.A. Gilbertson et al.

    Permeation of calcium ions through non-NMDA glutamate channels in retinal bipolar cells

    Science

    (1991)
  • R. Gill et al.

    Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil

    J. Neurosci.

    (1987)
  • Cited by (249)

    • Neuroprotective effect of agomelatine in rat model of psychosis: Behavioural and histological evidence

      2021, Journal of Affective Disorders Reports
      Citation Excerpt :

      Further sections were stained with Haematoxylin and Eosin. Hippocampus (CA1 – CA3) and BLA neuron numbers were quantified with Motic Images Advanced software (Buchan et al., 1991. A 10-counting grid 10 × 10 μm was used to obtain reference square of 100 μm.

    • 3-Hydroxy-1H-quinazoline-2,4-dione derivatives as new antagonists at ionotropic glutamate receptors: Molecular modeling and pharmacological studies

      2012, European Journal of Medicinal Chemistry
      Citation Excerpt :

      We cannot exclude that the preventive effects of compound 3 on AD appearance and loss of neurotransmission induced by OGD could be related to the AMPA receptor blockade that was demonstrated to counteract AD appearance during OGD in hippocampal CA1 region [49]. Interestingly, specific antagonists of the KA receptor GluK2 subunit and of AMPA receptor are protective in cerebral ischemia models, both in vivo and in vitro [50–54]. The studies described in the present work have clarified the SARs of the 3-hydroxyquinazolin-2-4-dione series as iGluRs antagonists.

    View all citing articles on Scopus

    This work was supported by the NIH Grant NS-03346, The Heart and Stroke Foundation of Ontario, and a Canadian Heart Foundation Scholarship to A.M.B.

    1

    We thank Dr. Tage Honore of Novo Nordisk for samples pf NBQX.

    View full text